Expression of apoptosis-regulating genes in the rat prostate following botulinum toxin type a injection
1 Department of Urology, Hospital de São João, Alameda Professor Hernâni Monteiro, 4200-319, Porto- Portugal
2 Institute for Molecular and Cell Biology (IBMC), Rua do Campo Alegre, 823, 4150-180 Porto - Portugal
3 Department of Experimental Biology, Faculty of Medicine-University of Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto- Portugal
4 Faculty of Nutrition and Food Sciences, Alameda Professor Hernâni Monteiro, 4200-319, Porto- Portugal
5 Faculty of Medicine-University of Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto- Portugal
BMC Urology 2012, 12:1 doi:10.1186/1471-2490-12-1Published: 4 January 2012
Onabotulinumtoxin A (OnabotA) injection has been investigated as a novel treatment for benign prostatic enlargement caused by benign prostatic hyperplasia. An OnabotA - induced volume reduction caused by sympathetic fibers impairment has been proposed as a potential mechanism of action. Our aim was to investigate the expression of apoptosis-regulating proteins in the rat prostate following OnabotA intraprostatic injection.
Adult Wistar rats were injected in the ventral lobes of the prostate with 10 U of OnabotA or saline. A set of OnabotA-injected animals was further treated with 0.5 mg/kg of phenylephrine (PHE) subcutaneously daily. All animals were sacrificed after 1 week and had their prostates harvested. Immunohistochemical staining was performed for Bax, Bcl-xL and caspase-3 proteins and visualized by the avidin-biotin method. The optical density of the glandular cells was also determined, with measurement of differences between average optical densities for each group.
Saline-treated animals showed intense epithelial staining for Bcl-xL and a faint labelling for both Bax and Caspase-3. OnabotA-treated rats showed a reduced epithelial staining of Bcl-xL and a consistently increased Bax and Caspase-3 staining when compared with saline-treated animals. PHE-treated animals showed a stronger Bcl-xL staining and reduced staining of both Bax and Caspase-3 when compared to the OnabotA group. Mean signal intensity measurements for each immunoreaction confirmed a significant decrease of the signal intensity for Bcl-xL and a significant increase of the signal intensity for Bax and Caspase 3 in OnabotA-injected animals when compared with the control group. In OnabotA+PHE treated animals mean signal intensity for Bcl-xL, Bax and Caspase 3 immunoreactions was identical to that of the control animals.
These results support the hypothesis that OnabotA activates apoptotic pathways in the rat prostate through a mechanism that involves sympathetic outflow impairment.